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Activated integrins identify functional antigen-specific CD8+ T cells within minutes after antigen stimulation.

ABSTRACT: Immediate ?2-integrin activation upon T cell receptor stimulation is critical for effective interaction between T cells and their targets and may therefore be used for the rapid identification and isolation of functional T cells. We present a simple and sensitive flow cytometry-based assay to assess antigen-specific T cells using fluorescent intercellular adhesion molecule (ICAM)-1 multimers that specifically bind to activated ?2-integrins. The method is compatible with surface and intracellular staining; it is applicable for monitoring of a broad range of virus-, tumor-, and vaccine-specific CD8+ T cells, and for isolating viable antigen-reacting cells. ICAM-1 binding correlates with peptide-MHC multimer binding but, notably, it identifies the fraction of antigen-specific CD8+ T cells with immediate and high functional capability (i.e., expressing high levels of cytotoxic markers and cytokines). Compared with the currently available methods, staining of activated ?2-integrins presents the unique advantage of requiring activation times of only several minutes, therefore delivering functional information nearly reflecting the in vivo situation. Hence, the ICAM-1 assay is most suitable for rapid and precise monitoring of functional antigen-specific T cell responses, including for patient samples in a variety of clinical settings, as well as for the isolation of functional T cells for adoptive cell-transfer immunotherapies.

SUBMITTER: Dimitrov S

PROVIDER: S-EPMC6004473 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Activated integrins identify functional antigen-specific CD8+ T cells within minutes after antigen stimulation.

Dimitrov Stoyan S Gouttefangeas Cécile C Besedovsky Luciana L Jensen Anja T R ATR Chandran P Anoop PA Rusch Elisa E Businger Ramona R Schindler Michael M Lange Tanja T Born Jan J Rammensee Hans-Georg HG

Proceedings of the National Academy of Sciences of the United States of America 20180529 24

Immediate β2-integrin activation upon T cell receptor stimulation is critical for effective interaction between T cells and their targets and may therefore be used for the rapid identification and isolation of functional T cells. We present a simple and sensitive flow cytometry-based assay to assess antigen-specific T cells using fluorescent intercellular adhesion molecule (ICAM)-1 multimers that specifically bind to activated β2-integrins. The method is compatible with sur ...[more]

PMID: 29844168

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Activated integrins identify functional antigen-specific CD8+ T cells within minutes after antigen stimulation.

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Activated integrins identify functional antigen-specific CD8<sup>+</sup> T cells within minutes after antigen stimulation.

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